Dr Pia Ostergaard’s research focus mainly lies within lympho-vascular medicine.
The lymphatic system is important for fluid homeostasis but also has a critical immunological function, particularly with regard to infection. In addition, it plays a major role in cancer progression.
Lymphatic malformation or dysfunction can lead to Primary Lymphoedema, which is an inherited form of this disorder. Primary Lymphoedema is clinically and genetically heterogeneous and is caused by defects in the lymphatic system that lead to swelling of one or more limbs or other parts of the body. It is a rare disorder (1.15 in 100,000 less than 20 years) and in the more extreme forms can increase mortality, especially in infants.
Lymphoedema is a lifelong, often disabling condition associated with a high morbidity with distressing swelling of the affected limbs, recurrent cellulitis, discomfort and significant skin changes. Treatment is limited to compression garments and manual lymphatic drainage. Many patients find Primary Lymphoedema debilitating, embarrassing, stressful and painful leading to considerable psychological morbidity.
Dr Ostergaard’s research group has focused on the genetic causes of lymphatic failure. Seven genes have recently been identified by the group: EPHB4, GATA2, GJA1, GJC2, KIF11, PIEZO1, and VEGFC in seven clinically homogenous phenotypic sub-classifications of Primary Lymphoedema using exome sequencing techniques. Finding the genetic causes of lymphatic dysfunction in Primary Lymphoedema, increases our understanding of the development of the lymphatic system, and our results feed into the basic research on the lymphovascular system.
There still remain numerous Primary Lymphoedema patients where a genetic cause is yet to be identified. The identification of further disease causing genes is crucial in understanding the molecular pathways and mechanisms involved in disease pathogenesis, and will ultimately lead to the formation of novel and more effective treatments. Genetic advances in Primary Lymphoedema will also benefit patients through accurate molecular diagnosis.
Following a career break (2002-2005) to bring up children, Dr Ostergaard was appointed Daphne Jackson Fellow (part-time) at St George's, betwen 2005 and 2007. This was sponsored by the Daphne Jackson Trust and the Medical Research Council
In 2007, Dr Ostergaard was appointed as a postdoctoral researcher at St George's, funded by the British Skin Foundation and the British Heart Foundation. Following this Dr Ostergaard was promoted to Lecturer in Human Genetics in 2013 and Senior Lecturer in 2015. Her research focus mainly lies within lymphovascular medicine.
Dr Ostergaard gained her PhD from the Natural History Museum and Imperial College London (2004) under the supervision of Professor GA Boxshall and Professor D Quicke.
Since 2008 Dr Ostergaard has been working for the Daphne Jackson Trust as an advisor. Her experience as a past Daphne Jackson Fellow enables her to assist the Trust with those activities related to the Fellowship selection process.
For full list of publications, see Dr Ostergaard's Research Gate profile.
For reprints see the St George's Online Research Archive (SORA).
Martin-Almedina S, Martinez-Corral I, Holdhus R, Vicente A, Fotiou E, Lin S, Petersen K, Simpson MA, Hoischen A, Gilissen C, Jeffery H, Atton G, Karapouliou C, Brice G, Gordon K, Wiseman JW, Wedin M, Rockson SG, Jeffery S, Mortimer PS, Snyder MP, Berland S, Mansour S, Makinen T, Ostergaard P. (2016).EPHB4 kinase-inactivating mutations cause autosomal dominant lymphatic-related hydrops fetalis. J Clin Invest. 126(8):3080-8.
Fotiou E, Martin-Almedina S, Simpson MA, Lin S, Gordon K, Brice G, Atton G, Jeffery I, Rees DC, Mignot C, Vogt J, Homfray T, Snyder MP, Rockson SG, Jeffery S, Mortimer PS, Mansour S, Ostergaard P. (2015). Novel mutations in PIEZO1 cause an autosomal recessive generalized lymphatic dysplasia with non-immune hydrops fetalis. Nat Commun. 6:8085.
Joyce S, Gordon K, Brice G, Ostergaard P, Nagaraja R, Short J, Moore S, Mortimer P, Mansour S. (2015).The lymphatic phenotype in Noonan and Cardiofaciocutaneous syndrome. Eur J Hum Genet. 24(5):690-696.
Atton G, Gordon K, Brice G, Keeley V, Riches K, Ostergaard P, Mortimer PS, Mansour S (2015). The lymphatic phenotype in Turner syndrome: an evaluation of nineteen patients and literature review.Eur J Hum Genet. doi: 10.1038/ejhg.2015.41. [Epub ahead of print]
Jones GE*, Ostergaard P*, Moore AT, Connell FC, Williams D, Quarrell O, Brady AF, Spier I, Hazan F, Moldovan O, Wieczorek D, Mikat B, Petit F, Coubes C, Saul RA, Brice G, Gordon K, Jeffery S, Mortimer PS, Vasudevan PC, Mansour S. (2014). Microcephaly with or without chorioretinopathy, lymphoedema or mental retardation (MCLMR); review of phenotype associated with KIF11 mutations. Eur. J. Hum. Genet. 22:881-887.
Gordon K, Schulte D, Brice G, Simpson MA, Roukens MG, van Impel AW, Connell F, Kalidas K, Jeffery S, Mortimer PS, Mansour S, Schulte-Merker S, Ostergaard P. (2013). A Mutation in VEGFC, a Ligand for VEGFR3, is Associated with Autosomal Dominant Milroy-like Primary Lymphedema. Circ Res., 112(6):956-60.
Gordon K, Spiden SL, Connell FC, Brice G, Cottrell S, Short J, Taylor R, Jeffery S, Mortimer PS, Mortimer PS, Mansour S, Ostergaard P. (2013). FLT4/VEGFR3 and Milroy Disease: Novel Mutations, a Review of published variants and database update. Hum. Mutat, 34:23-31.
Connell FC, Gordon K, Brice G, Keeley V, Jeffery S, Mortimer PS, Mansour S, Ostergaard P (2013). The Classification and Diagnostic Algorithm for Primary Lymphatic Dysplasia: an update from 2010 to include molecular findings. Clin. Genet. 84:303-14.
Ostergaard P, Simpson MA, Mendola A, Vasudevan P, Connell FC, van Impel A, Moore AT, Loeys BL, Ghalamkarpour A, Onoufriadis A, Martinez-Corral I, Devery S, Leroy JG, van Laer L, Singer A, Bialer MG, McEntagart M, Quarrell O, Brice G, Trembath RC, Schulte-Merker S, Makinen T, Vikkula M, Mortimer PS, Mansour S, Jeffery S. (2012). Mutations in KIF11 cause autosomal-dominant microcephaly variably associated with congenital lymphedema and chorioretinopathy. Am J Hum Genet, 90:356-362.
Ostergaard P*, Simpson MA*, Connell FC, Steward CG, Brice G, Woollard WJ, Dafou D, Kilo T, Smithson S, Lunt P, Murday VA, Hodgson S, Keenan R, Pilz DT, Martinez-Corrall I, Makinen T, Mortimer PS, Jeffery S, Trembath RC, Mansour S. (2011). Mutations in GATA2 cause primary lymphoedema associated with a predisposition to acute myeloid leukemia (Emberger syndrome). Nat Genet 43:929-931.
At St George's Hospital Dr Ostergaard and colleagues have developed a nationwide lymphovascular clinical service with over 15 years of experience. The paediatric and primary lymphoedema clinic is a national tertiary referral service and has now collected DNA from over 1000 phenotyped cases of primary lymphoedema.
The Lymphovascular Research Unit (LRU) is a close collaboration between the clinicians and consultants in the St George's Hospital Primary Lymphoedema Clinic and a group of researchers in the Institute of Molecular and Clinical Sciences.
The LRU has the following members:
- Professor Peter Mortimer
- Professor Sahar Mansour
- Dr Kristiana Gordon
- Mr Glen Brice
- Professor Steve Jeffery
- Dr Silvia Martin-Almedina
- Dr Ines Martinez-Corral (at Uppsala University with our collaborator Dr Makinen)
- Miss Christina Karapouliou
- Miss Noeline Nadarajah
Pilot study into the genetics of Lipoedema from the Lipedema Foundation. March 2016 (two years).
PhD studentship from the British Heart Foundation. January 2016 (three years).
Start-up grant from theNoonan Syndrome Associaton. August 2014 (two years).
Functional Analysis of GATA2 and KIF11; newly identified genes for primary lymphoedema.British Heart Foundation. Jan 2014 (five years).
Analysis of candidate genes for Primary Lymphoedema identified by Next Generation Sequencing.Newlife foundation for disabled children.Oct 2013 (two years).